Funding is requested to upgrade a 12-year-old 600 MHz MR spectrometer with a Bruker Biospin AVANCE IIINMR Console, quadruple resonance inverse detection QCI CryoProbe, and SampleJet automated sample changer. The requested equipment will be installed on an existing Bruker Spectrospin actively shielded 14.1 T magnet. The requested upgrades of the 600 MHz NMR spectrometer are essential both to the particular aims of the NIH-funded research of the major users of the spectrometer and to the long-term goal of Columbia University to build upon its existing strengths in biological sciences, structural biology and biophysics, and clinical research. Research conducted on the 600 MHz instrument ranges from fundamental studies of structure/function of biomolecules, for example involved in DNA repair, to analysis of biomarkers in normal and pathological tissues, to discovery of novel lead compounds to pharmaceutical applications. Each of the three components of the requested equipment provides significant improvements in performance that in their entirety will dramatically enhance the capabilities of the 600 MHz NMR spectrometer to conduct this research.